Group-housed male mice exhibit aggressive behaviour towards their cage mates and form a social hierarchy. Here, we describe how social hierarchy in standard group-housed conditions affects behaviour and gene expression in male mice. Four male C57BL/6 mice were kept in each cage used in the study, and the social hierarchy was determined from observation of video recordings of aggressive behaviour. After formation of a social hierarchy, the behaviour and hippocampal gene expression were analysed in the mice. Higher anxiety- and depression-like behaviours and elevated gene expression of hypothalamic corticotropin-releasing hormone and hippocampal serotonin receptor subtypes were observed in subordinate mice compared with those of dominant mice. These differences were alleviated by orally administering fluoxetine, which is an antidepressant of the selective serotonin reuptake inhibitor class. We concluded that hierarchy in the home cage affects behaviour and gene expression in male mice, resulting in anxiety- and depression-like behaviours being regulated differently in dominant and subordinate mice.

Many animal species have been domesticated over the course of human history and became tame as a result of domestication. Tameness is a behavioral characteristic with 2 potential components: (1) reluctance to avoid humans and (2) motivation to approach humans. However, the specific behavioral characteristics selected during domestication processes remain to be clarified for many species. To quantify these 2 different components of tameness separately, we established 3 behavioral tests: the ‘active tame’, ‘passive tame’ and ‘stay-on-hand’ tests. We subjected genetically diverse mouse strains to these tests, including 10 wild strains (BFM/2Ms, PGN2/Ms, HMI/Ms, BLG2/Ms, NJL/Ms, KJR/Ms, SWN/Ms, CHD/Ms, MSM/Ms and CAST/Ei), a fancy strain (JF1/Ms) and 6 standard laboratory strains (C3H/HeNJcl, CBA/J, BALB/cAnNCrlCrlj, DBA/2JJcl, 129+Ter/SvJcl and C57BL/6JJcl). To analyze the effects of domestication, these 17 strains were divided into 2 groups: domesticated strains (fancy and laboratory strains) and wild strains. Significant differences between strains were observed in all traits, and the calculated estimates of broad-sense heritability were 0.15–0.72. These results illustrate that tameness in mice is significantly influenced by genetic background. In addition, they clearly show the differences in the features of tameness in domesticated and wild strains. Most of the domesticated strains showed significantly greater reluctance to avoid humans than wild strains, whereas there was no significant difference in the level of motivation to approach humans between these 2 groups. These results might help to clarify the genetic basis of tameness in mice.

Tameness is a major behavioral factor for domestication, and can be divided into two potential components: motivation to approach humans (active tameness) and reluctance to avoid humans (passive tameness). We identified genetic loci for active tameness through selective breeding, selection mapping, and association analysis. In previous work using laboratory and wild mouse strains, we found that laboratory strains were predominantly selected for passive tameness but not active tameness during their domestication. To identify genetic regions associated with active tameness, we applied selective breeding over 9 generations for contacting, a behavioural parameter strongly associated with active tameness. The prerequisite for successful selective breeding is high genetic variation in the target population, so we established and used a novel resource, wild-derived heterogeneous stock (WHS) mice from eight wild strains. The mice had genetic variations not present in other outbred mouse populations. Selective breeding of the WHS mice increased the contacting level through the generations. Selection mapping was applied to the selected population using a simulation based on a non-selection model and inferred haplotype data derived from single-nucleotide polymorphisms. We found a genomic signature for selection on chromosome 11 containing two closely linked loci.